Detection of microRNA expression in human peripheral blood microvesicles.
Detection of microRNA expression in human peripheral blood microvesicles.
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DOI：
10.1371/journal.pone.0003694
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Marsh, Clay B.
中科院分区：
文献类型：
--
作者：
Hunter, Melissa Piper;Ismail, Noura;Zhang, Xiaoli;Aguda, Baltazar D.;Lee, Eun Joo;Yu, Lianbo;Xiao, Tao;Schafer, Jeffrey;Lee, Mei-Ling Ting;Schmittgen, Thomas D.;Nana-Sinkam, S. Patrick;Jarjoura, David;Marsh, Clay B.
MicroRNAs(MiRNA)是一种小的非编码RNA，调节mRNA和蛋白质的翻译。MiRNAs的缺失或表达增强与包括癌症在内的几种疾病有关。然而，健康献血者中循环miRNA的鉴定还没有得到很好的描述。微泡，也被称为外周小体或微粒，在外周血液中循环，可以刺激细胞信号。在这项研究中，我们假设在正常的健康条件下，微囊含有miRNAs，有助于生物动态平衡。从正常健康人血浆中分离出微囊泡。从微泡和匹配的单个核细胞中提取RNA，并通过实时荧光聚合酶链式反应分析420个已知的成熟miRNAs。数据集的分级聚类表明，外周血单个核细胞(PBMC)和血浆微囊中miRNA的表达存在显著差异。我们观察到71个miRNAs在微泡和PBMC之间共表达。值得注意的是，我们发现分别有33个和4个miRNAs在血浆微泡和单个核细胞中显著差异表达。预测受检测到的miRNAs调控的基因靶点和相关的生物通路。在血液中的微囊中表达的miRNAs大多数被预测为调节血细胞的细胞分化和代谢途径。有趣的是，一些精选的miRNAs也被预测为免疫功能的重要调节器。本研究首次发现并确定了正常受试者循环血浆微泡中miRNA的表达。这项研究产生的数据为未来的研究提供了基础，以确定外周血miRNA特征在人类疾病中的预测作用，并将使定义这些miRNA调控的生物过程成为可能。
MicroRNAs (miRNA) are small non-coding RNAs that regulate translation of mRNA and protein. Loss or enhanced expression of miRNAs is associated with several diseases, including cancer. However, the identification of circulating miRNA in healthy donors is not well characterized. Microvesicles, also known as exosomes or microparticles, circulate in the peripheral blood and can stimulate cellular signaling. In this study, we hypothesized that under normal healthy conditions, microvesicles contain miRNAs, contributing to biological homeostasis. Microvesicles were isolated from the plasma of normal healthy individuals. RNA was isolated from both the microvesicles and matched mononuclear cells and profiled for 420 known mature miRNAs by real-time PCR. Hierarchical clustering of the data sets indicated significant differences in miRNA expression between peripheral blood mononuclear cells (PBMC) and plasma microvesicles. We observed 71 miRNAs co-expressed between microvesicles and PBMC. Notably, we found 33 and 4 significantly differentially expressed miRNAs in the plasma microvesicles and mononuclear cells, respectively. Prediction of the gene targets and associated biological pathways regulated by the detected miRNAs was performed. The majority of the miRNAs expressed in the microvesicles from the blood were predicted to regulate cellular differentiation of blood cells and metabolic pathways. Interestingly, a select few miRNAs were also predicted to be important modulators of immune function. This study is the first to identify and define miRNA expression in circulating plasma microvesicles of normal subjects. The data generated from this study provides a basis for future studies to determine the predictive role of peripheral blood miRNA signatures in human disease and will enable the definition of the biological processes regulated by these miRNA.
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